There is a long-standing interest in manipulating cells of the immune system to achieve control of autoimmune disease. While targeted antigen-specific therapy remains of great interest, there has also been considerable development of polyclonal, or non-antigen specific therapies. In addition to general immunosuppression, e.g. through the use of agents such as hydrocortisone, many therapies are now being brought to the clinic that provide for a more selective modification of the immune system, such as modulation of cytokines.
Multiple sclerosis (MS) is the most common autoimmune illness of the central nervous system. For many years the inflammatory manifestations of MS were treated using only corticosteroids. However, more recently the results of clinical trials with immunomodulatory agents have changed the therapeutic approach to this disease. Interferon beta (IFNβ)-1b represents the pioneer of those therapies. There is growing evidence from clinical trials on relapsing-remitting MS and clinically isolated syndromes suggestive of MS that IFNβ-1b reduces the frequency and severity of relapses and the development of new and active brain lesions. There can be a significant benefit to treatment early in the disease, for example as shown by the Betaferon/Betaseron in Newly Emerging Multiple Sclerosis For Initial Treatment (BENEFIT) study. Irreversible axonal damage can begin early in the course of MS, and immunomodulatory treatment of MS can have a greater effect early in the disease course.
A downside to this promising therapy is the diversity of responses in patient populations. While a significant proportion of patients can respond to a particular therapy, many do not. The clinician can therefore need to prescribe sequential expensive and time-consuming therapies in order to determine which is effective for the individual patient. Furthermore, it has been reported that IFN-β can exacerbate symptoms in some individuals.
The use of disease-modifying therapies in autoimmune conditions is of great clinical interest; however these therapies suffer from the inability to determine using a blood test whether a patient's immune system is responding appropriately to treatment. The present invention addresses this need.
Publications of interest include Ramgolam et al. (2011) J Immunol. 186(7):4518-26, entitled “B cells as a therapeutic target for IFN-β in relapsing-remitting multiple sclerosis”; Meinl et al. (2011) J Neurol Sci. 306(1-2):180-2, entitled ‘Humoral autoimmunity in multiple sclerosis’; Krumbholz et al. (2008) Brain 131(Pt 6):1455-63, entitled ‘Interferon-beta increases BAFF levels in multiple sclerosis: implications for B cell autoimmunity’; Quan et al. (2012) Mult. Sclerosis, entitled ‘Impaired regulatory function and enhanced intrathecal activation of B cells in neuromyelitis optica: distinct from multiple sclerosis’; and Thangarajh et al. (2007) Scand J Immunol. 65(5):461-6, entitled ‘The expression of BAFF-binding receptors is not altered in multiple sclerosis or myasthenia gravis’.